Project Summary The goal of this proposal is to make significant advancements in our understanding of resident memory T cell (TRM) biology that will inform mechanisms of immunity and vaccination. TRM longevity and stability will be rigorously examined. Moreover, the proposal will test the hypothesis that TRM exhibit developmental plasticity and retrograde migration, giving rise to cells contained within circulating T cell populations that are significantly advantaged to reconstitute TRM-based immunity specifically at their previous site of residence. Lastly, the ontogeny and function of lymph node TRM will be defined.